a phase ib trial of a maintenance multipeptide vaccine (s-588210) in patients with unresectable malignant pleural mesothelioma without progression after first-line chemotherapy

Conditions: Malignant Pleural Mesothelioma (MPM)

Summary: a phase ib study investigating the safety, the immunogenicity and the optimal administration frequency of the s-588210 5-peptide vaccine in mpm patients without progression after pemetrexed-based chemotherapy will be conducted. additionally, to identify more accurate predictive biomarkers of response to s-588210, t-cell-receptor-sequencing (tcr) pre- and post-vaccination will be performed in blood samples of patients treated with the vaccine. immunohistochemical analysis of the vaccine oncoantigens will also be correlated with induction of antigen-specific t-cell responses. finally, to explore the infiltration of tumors with t-cells and the potential presence of an immunosuppressive tumor microenvironment, immunohistochemistry for immune checkpoints (including pdl1/pd1, ctla4) and immune suppressive cell subsets (t-regs, macrophages) will be performed.

primary objective: to evaluate the rate of peptide-specific ctl induction to s-588210 within the first 8 months in hla-a\*02:01-positive patients with mpm who have not progressed on first-line pemetrexed-based chemotherapy treated on a weekly or every other week vaccination schedule. secondary objectives: 1. to evaluate the safety of s-588210 in hla-a\*02:01-positive patients with mpm treated with s-588210 2. to determine the disease control rate (dcr) in hla-a\*02:01-positive patients with mpm treated with s-588210 3. to determine the progression-free-survival (pfs) in hla-a\*02:01-positive patients with mpm who have not progressed on first-line pemetrexed-based chemotherapy and who are treated with s-588210 4. to evaluate the peptide-specific ctl response to s-588210 over time up to 8 months in hla-a\*02:01-positive patients with mpm who have not progressed on first-line pemetrexed-based chemotherapy

Eligibility criteria:
inclusion criteria: * patients with unresectable mpm that have completed 4-6 cycles of standard first-line pemetrexed-based chemotherapy for at least 1 month and have not progressed * age\>18 * able to provide informed consent for the study * hla-a\*02:01 positive * ecog ps=0-1 at enrollment * measurable indicator lesion by modified recist criteria * adequate bone marrow (anc \> 1000cells/ml, plt \> 50,000/ml, hg \> 8gr/dl), renal (cr \> 2.5xunl) and liver function (ast, alt\< 3x unl, total bilirubin \< 2x unl, alp \< 3x unl) * archival tumor tissue available for ihc (1 paraffin-embedded block) * epithelioid or biphasic histology exclusion criteria: * chemotherapy or investigational antineoplastic drug within 1 month of planned initiation of vaccine therapy * patients who received depdc1, mphosph1, urlc10, cdca1, or koc1 peptide vaccines before * active treatment with corticosteroids or other immunosuppressive agents * patients who are expected to require any of the following therapies between enrollment and completion or discontinuation of the study treatment: 1. immunosuppressive drugs, including corticosteroids, methotrexate, mercaptopurine, azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, atg (anti-thymoglobulin), il2-receptor antibodies (basiliximab, daclizumab), tnf-a antibodies (infliximab, etanercept, adalimumab) 2. radiotherapy for the target disease 3. surgical therapy for the target disease * history of bone marrow transplantation * active infection * human immunodeficiency virus infection * history of or active systemic autoimmune disorder or immunodeficiency syndromes * history of severe (ctcae v.4.03 grade 3 or higher) allergic reaction to a drug, vaccination, or biological preparation. * pregnancy * patients who cannot or do not intend to practice effective contraception * severe illness requiring hospitalization * lymphocytes \<15% of total wbcs at baseline * sarcomatoid histology * severe (ctcae v.4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease

Keywords: mesothelioma multipeptide vaccine s-588210